polygenic adaptation

Casto AM & Feldman MW 2011 Genome-wide association study SNPs in the Human Genome Diversity Project populations: does selection affect unlinked SNPs with shared trait associations? PLoS Genet 7:e1001226.

  • given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci
  • a possibility which has yet to be explored empirically
  • empirical studies have found only a few examples of variants that have undergone "hard sweeps", where a favored allele arises by mutation and increases to high frequency in a population
  • adaptation to new phenotypic optima may proceed through small allele frequency changes at many polymorphic loci
  • selection on traits need not be limited to positive selection
  • selection acts on traits not only to achieve new phenotypic optima, but also to maintain those optima once they have been reached, perhaps through balancing or negative selection
  • there is solid evidence that these study groups represent instances of a polygenic response to selective pressure on an associated trait
  • epistasis may be widespread among polymorphic sites in the human genome and can be difficult to detect, particularly as the number of putatively interacting loci considered increases
  • epistasis has been frequently found to exist between loci in model organisms like flies and mice
  • many, even most, GWAS SNPs are associated with more than one trait
  • like epistasis, pleiotropy has been found to be common for variants influencing complex traits in model organisms
  • we found multiple instances of it in the dataset that we studied here
  • the presence of epistasis and pleiotropy can mean that the response of a variant to selection is dependent on the genetic background and the existence and strength of selection on other traits
  • complexities we did not account for in our analysis
  • recent work has proposed negative selection as one explanation for what appear to be common non-neutral patterns of variation in the human genome, such as the elevation of Fst values in genes and the reduction of diversity at sites linked to coding and regulatory regions
  • our results suggest that both negative and positive selection may influence variation at GWAS SNPs
  • their relative contributions, however, remain unclear